Abstract 25P
Background
The open-label, phase III global POSEIDON study (NCT03164616) evaluated first-line durvalumab (D) with or without tremelimumab (T) plus chemotherapy (CT) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC). At the final analysis of the global study population D+T+CT demonstrated statistically significant improvements in both progression-free survival (PFS; HR 0.72; 95% CI 0.60–0.86; p=0.0003) and overall survival (OS; HR 0.77; 95% CI 0.65–0.92; p=0.0030) vs CT alone, leading to approvals for this regimen. D+CT significantly improved PFS vs CT (0.74; 95% CI 0.62–0.89; p=0.0009), with a positive trend for OS improvement (HR 0.86; 95% CI 0.72–1.02; p=0.0758). Prespecified exploratory analyses were conducted in an extended cohort enrolled in China.
Methods
Pts with EGFR/ALK wild-type mNSCLC were randomised 1:1:1 to first-line treatment with: D (until progression) ± limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles); or CT (up to 6 cycles). Primary endpoints were PFS and OS for D+CT vs CT. Key secondary endpoints were PFS and OS for D+T+CT vs CT.
Results
175 pts were randomised in China. 30.3% had PD-L1 tumour cell ≥50%, 48.0% had stage IVB disease and 48.6% had squamous histology. Distribution of CT regimens across arms was generally balanced (Table). At the data cutoff for the final analysis of PFS and interim analysis of OS (30 April 2024; median [range] follow-up for OS in censored pts: 24.1 [0–42.1] months), PFS and OS were numerically improved by both D+T+CT and D+CT vs CT (Table). Treatment-related adverse events (TRAEs) were maximum grade 3/4 in 65.5%, 62.3% and 49.1% and led to death in 5.2%, 0% and 0% of pts receiving D+T+CT, D+CT and CT, respectively; 22.4%, 11.3% and 12.3%, respectively, discontinued treatment because of TRAEs.
Table 25P| D+T+CT | D+CT | CT | |
| CT regimen received (safety analysis set) | |||
| Pts, n | 58 | 53 | 57 |
| Pemetrexed doublet, n (%) | 29 (50.0) | 30 (56.6) | 25 (43.9) |
| Gemcitabine doublet, n (%) | 29 (50.0) | 23 (43.4) | 32 (56.1) |
| Efficacy outcomes (ITT population) | |||
| Pts, n | 58 | 55 | 62 |
| Median PFS (95% CI), mo | 6.6 (4.6, 10.1) | 6.3 (4.4, 8.5) | 4.8 (3.7, 6.4) |
| 12-mo PFS rate, % | 28.8 | 29.1 | 7.3 |
| PFS HR (95% CI) vs CT | 0.56 (0.36, 0.89) | 0.61 (0.39, 0.97) | |
| Median OS (95% CI), mo | 16.3 (11.5, NR) | 21.6 (11.7, 27.1) | 16.8 (13.3, 22.5) |
| 24-mo OS rate, % | 39.2 | 41.6 | 30.9 |
| OS HR (95% CI) vs CT | 0.81 (0.51, 1.29) | 0.82 (0.51, 1.30) | |
ITT, intention-to-treat; mo, months; NR, not reached.
Conclusions
Overall, efficacy and safety of D+T+CT and D+CT vs CT in the China cohort were generally consistent with the final results of the POSEIDON global study.
Clinical trial identification
NCT03164616; release date: 23 May 2017.
Editorial acknowledgement
Medical writing support for this abstract, under the direction of the authors, was provided by Simon Lancaster BSc of Ashfield MedComms, an Inizio company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
X. Geng: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. C. Lowery: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M.L. Johnson: Financial Interests, Personal, Principal Investigator: AbbVie, Adaptimmune, Amgen, Arcus Biosciences, Array BioPharma, ArriVent BioPharma, Artios Pharma, AstraZeneca, Bayer, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Cit, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immu, Kartos Therapeutics, LockBody Therapeutics, Loxo Oncology, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, NextPoint Therapeutics, Novartis, Numab Therapeutics, Nuvalent, OncoC4, Palleon P, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeuti, Takeda Pharmaceuticals, TCR2 Therapeutics, Tempest Therapeutics, TheRas, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, Vividion, Vyriad, Y-mAbs Therapeutics; Financial Interests, Personal, Advisory Role: AbbVie, Alentis Therapeutics, Amgen, Arcus Biosciences, AstraZeneca, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio Limited, Daiichi Sankyo, Fate Therapeutics, Genentech/Roche, Gilead Sciences, GSK, Gritstone On, Jazz Pharmaceuticals, Lilly, Merck, Mirati Therapeutics, ModeX Therapeutics, Normunity, Novartis, Novocure, Pfizer, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Zai Laboratory. All other authors have declared no conflicts of interest.